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Trial record 1 of 1 for:    NCT00702884
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Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer

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ClinicalTrials.gov Identifier: NCT00702884
Recruitment Status : Completed
First Posted : June 20, 2008
Results First Posted : March 21, 2017
Last Update Posted : March 21, 2017
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE June 19, 2008
First Posted Date  ICMJE June 20, 2008
Results First Submitted Date  ICMJE February 4, 2016
Results First Posted Date  ICMJE March 21, 2017
Last Update Posted Date March 21, 2017
Actual Study Start Date  ICMJE June 30, 2008
Actual Primary Completion Date September 17, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
Progression-free Survival Rate [ Time Frame: up to 24 weeks ]
Complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2008)
Progression-free survival rate (complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
  • Overall Response Rate [ Time Frame: up to 4 years ]
    The Overall Response Rate (ORR) was assessed using Partial Response + Complete Response for patients. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
  • Median Overall Survival Time [ Time Frame: up to 4 years ]
    The median overall survival time will be reported using the 95% confidence intervals for the parameters.
  • Median Progression-free Survival Time [ Time Frame: up to 4 years ]
    Progression free survival was measured as the time from start of treatment to the first measurement of tumor growth.
  • Frequency and Severity of Adverse Events [ Time Frame: up to 4 years ]
    The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for adverse event reporting.
  • Change in Mean Vessel Density [ Time Frame: up to 4 years ]
    Quantitative assessment of proliferating tumor cells, and apoptosis, of the laboratory and radiographic correlates, the analyses will be purely explorative.
  • Quantitative Assessment of Proliferating Tumor Cells and Apoptosis [ Time Frame: up to 4 years ]
    Biopsy sample taken from patients before and after treatment Apoptosis measures using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, which measures 3' nicked DNA. DNA is degraded in the early steps of apoptosis into low molecular weight (LMW) fragments and the production of single strand breaks in the high molecular weight DNA.Both of these features of apoptosis can be detected by labeling free 3'-OH termini with modified nucleotides, in our case this will be biotin-labeled dUTP. Terminal deoxynucleotidyl transferase (TdT) is an enzyme that labels blunt-ends of DNA breaks and can catalyze polymerization of nucleotides to free 3'-OH DNA ends in a template-independent manner. The newly incorporated nucleotides are detected by a secondary antibody, avidin-peroxidase. After substrate reaction, the stained cells can be detected and counted under a light microscope. Apoptotic cells will be fixed with formaldehyde which links LMW DNA
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2008)
  • Overall Response Rate
  • Median Overall Survival Time
  • Median Progression-free Survival Time
  • Frequency and Severity of Adverse Events
  • Change in Mean Vessel Density
  • Quantitative Assessment of Proliferating Tumor Cells and Apoptosis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer
Official Title  ICMJE A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers
Brief Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory esophageal or gastroesophageal junction cancer.

Detailed Description

OBJECTIVES:

Primary

  • To determine the progression-free survival rate (complete response, partial response, and stable disease as defined by RECIST criteria [Response Evaluation Criteria in solid Tumors]) at 24 weeks in patients with relapsed or refractory esophageal or gastroesophageal junction cancer treated with sunitinib malate.

Secondary

  • To explore the predictive role of a hybrid imaging protocol that combines PET/CT (Positron emission tomography) scan simultaneously with dynamic contrast-enhanced MRI.
  • Correlate quantitative changes in mean vessel density, alterations in tumor cell proliferation, and apoptosis in tumor biopsy specimens with clinical outcome in these patients.
  • To evaluate the objective response as defined by RECIST criteria, median overall survival, and median progression-free survival of these patients.
  • To evaluate the toxicities of sunitinib malate in these patients.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tumor tissue sample collection periodically for correlative laboratory studies. Tumor tissue samples are assessed by immunohistochemistry and TUNEL for detection and quantitation of mean vessel density, proliferating tumor cells, and apoptosis. Tumor tissue samples are also assessed by immunohistochemistry for MAPK levels. Blood samples are analyzed by ELISA for VEGF, PlGF, sVEGFR2, and sVEGFR3 levels. Patients also undergo PET/CT scan and dynamic contrast-enhanced MRI periodically for correlative studies.

After completion of study treatment, patients are followed for at least 6 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Cancer
Intervention  ICMJE Drug: sunitinib malate
Sunitinib 37.5 mg daily for a 4 week cycle
Other Names:
  • Sutent
  • SU011248 L-Malate salt
  • SU010398
  • PHA-290940AD
  • SU011248
Study Arms  ICMJE Experimental: Sunitinib
Sunitinib 37.5 mg daily for a 4 week cycle
Intervention: Drug: sunitinib malate
Publications * Wu C, Mikhail S, Wei L, Timmers C, Tahiri S, Neal A, Walker J, El-Dika S, Blazer M, Rock J, Clark DJ, Yang X, Chen JL, Liu J, Knopp MV, Bekaii-Saab T. A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers. Br J Cancer. 2015 Jul 14;113(2):220-5. doi: 10.1038/bjc.2015.197. Epub 2015 Jul 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 19, 2008)
25
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 30, 2013
Actual Primary Completion Date September 17, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed esophageal or gastroesophageal junction carcinoma that is not amenable to curative surgery or other curative therapy

    • Advanced, relapsed or refractory disease
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/μL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Serum calcium ≤ 12.0 mg/dL
  • Total bilirubin normal
  • AST (aspartate aminotransferase) and ALT (Alanine Aminotransferase) ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
  • No ongoing cardiac dysrhythmias ≥ grade 2, atrial fibrillation of any grade, or prolongation of the QTc (corrected QT interval) interval to > 450 msec (for males) or > 470 msec (for females)
  • No hypertension that cannot be controlled by medications (i.e., systolic/diastolic blood pressure > 150/100 mm Hg despite optimal medical therapy)
  • No myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
  • No cerebrovascular accident or transient ischemic attack within the past 12 months
  • No pulmonary embolism within the past 12 months
  • No condition that would impair the ability to swallow and retain sunitinib malate tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No pre-existing thyroid abnormality that cannot be maintained in the normal range with medication
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • Recovered from prior therapy
  • At least 4 weeks since prior radiotherapy or major surgery
  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C, carmustine, or alkylating agents)
  • No more than 6 prior courses of an alkylating agent
  • No more than 450 mg/m² of prior doxorubicin hydrochloride or 900 mg/m² of prior epirubicin hydrochloride
  • No more than 2 lines of prior therapy in the metastatic setting
  • No prior anti-VEGF monoclonal antibodies, such as bevacizumab or aflibercept
  • No prior tyrosine kinase inhibitors with similar targets (e.g., sorafenib tosylate or axitinib)
  • No other concurrent investigational agents
  • No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as warfarin

    • Warfarin at doses of ≤ 2 mg daily are allowed for prophylaxis of thrombosis
    • Low molecular weight heparin allowed provided PT/INR (Prothrombin time and international normalized ratio) is ≤ 1.5
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00702884
Other Study ID Numbers  ICMJE OSU-07121
NCI-2011-03148 ( Registry Identifier: Clinical Trials Reporting Program (CTRP) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Tony Bekaii-Saab
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Tanios Bekaii-Saab, MD Ohio State University
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP